Effects of genetic polymorphism G894T on endothelial nitric oxide synthase, on endothelial function, thrombosis/fibrinolysis system and inflammatory process, in young myocardial infarction survivors

Abstract

Genetic polymorphism G894T on endothelial nitric oxide synthase (eNOS), has been associated with increased risk of myocardial infarction (MI). However, its effects on endothelial function, thrombosis/fibrinolysis system and inflammatory process remain unknown. We investigated the effect of G894T polymorphism on endothelial function, thrombosis/fibrinolysis and inflammatory markers in young MI survivors. This study enrolled 60 young patients with a history of premature MI (mean age 45.2±4.2 years). All patients were in stable clinical condition for at least one year before recruitment. Endothelial function was evaluated in the forearm using venous occlusion strain-gauge plethysmography. Endothelium dependent dilation (EDD) and endothelium independent dilation (EID) were expressed as the %change of forearm blood flow from rest to the maximum flow during reactive hyperemia or after sublingual nitroglycerin administration respectively. The G894T polymorphism on eNOS gene was determined by polymerase chain reaction (PCR), while plasma levels of plasminogen activator inhibitor (PAI-1), vonWillebrand factor (vWF) and interleukin 1b (IL-1b) were measured with ELISA. Patients were divided into groups according to genotype. Twenty patients were G homozygotes, 31 were heterozygotes and 9 were T homozygotes. EDD was significantly higher in GG (113.1±14.5) compared GT (39.8±5.2%) or TT(41.1±3.3%). VWF was significantly higher in GT (65.5±2.5%) or TT(57.7±3.2) compared to GG (50.4±3.5%,p<0.05 for both). Carriers of the T allele had significantly lower EDD (p<0.01) and higher levels of vWF (p<0.05) compared to GG. Plasma PAI-1 and IL-1b were not significantly different between TT+GT (35.4±4.9ng/ml and 0.86±0.12 pg/ml) and GG (37.2±6.6 mg/dl and 0.84±0.13pg/ml respectively, p=NS for both). Carriers of the T allele have blunted endothelial function, and higher levels of von Willebrand factor one year after an incident of premature myocardial infarction. Therefore, G894T polymorphism on eNOS gene may affect endothelial function and thrombosis, in patients with premature myocardial infarction.